本文選題：三陰性乳腺癌 + 血管正�；���； 參考：《中國(guó)病理生理雜志》2017年10期

【摘要】：目的:通過(guò)觀察人三陰性乳腺癌(triple-negative breast cancer,TNBC)模型裸鼠血管正�；髮�(duì)紫杉醇的反應(yīng),探討重組人內(nèi)皮抑素與紫杉醇在血管正�；瘯r(shí)間窗內(nèi)聯(lián)用是否優(yōu)于紫杉醇單用并分析磁共振成像(magnetic resonance imaging,MRI)在早期評(píng)估化療的作用。方法:將人TNBC細(xì)胞株MDA-MB-231種植于36只BALB/c-nu雌性裸小鼠的右下腹部皮下,隨機(jī)分成4組(模型組、重組人內(nèi)皮抑素治療組、紫杉醇治療組及人內(nèi)皮抑素聯(lián)用紫杉醇治療組),每組有7只完成實(shí)驗(yàn)。重組人內(nèi)皮抑素于實(shí)驗(yàn)開(kāi)始時(shí)給藥,連續(xù)使用17 d,紫杉醇于實(shí)驗(yàn)第6天和第12天分別給藥,所有用藥均為腹腔注射,用量均為10 mg·kg~(-1)·d~(-1)。治療前1 d及注射實(shí)驗(yàn)試劑后5、11、17 d進(jìn)行MRI掃描,所有荷瘤鼠均在最后一次MRI掃描后頸椎脫位處死,切下瘤體,進(jìn)行病理學(xué)及免疫組化檢測(cè),測(cè)定腫瘤微血管密度(microvessel density,MVD)及Ki67表達(dá)。結(jié)果:第17天,聯(lián)用組移植瘤體積小于模型組及重組人內(nèi)皮抑素治療組(P0.05),但與紫杉醇治療組比較無(wú)顯著差異。第11天,紫杉醇治療組的慢彌散系數(shù)大于模型組,聯(lián)用組慢彌散系數(shù)大于重組人內(nèi)皮抑素治療組(P0.05)。解剖各組荷瘤鼠未見(jiàn)遠(yuǎn)處轉(zhuǎn)移病灶。HE染色顯示4組腫瘤外周均有明顯壞死,且藥物治療組壞死程度均高于模型組。藥物治療組的MVD均小于模型組,且藥物聯(lián)用組均小于藥物單用組(P0.05)。藥物聯(lián)用組Ki67表達(dá)較重組人內(nèi)皮抑素組明顯降低,但與紫杉醇治療組相比無(wú)顯著差異。結(jié)論:在血管正�；瘯r(shí)間窗內(nèi),重組人內(nèi)皮抑素聯(lián)合紫杉醇化療對(duì)TNBC移植瘤雖有明顯的抑瘤作用,但療效未優(yōu)于紫杉醇;慢彌散系數(shù)可以早期預(yù)測(cè)治療效果。
[Abstract]:Objective: to observe the response to paclitaxel in nude mice with triple-negative breast cancer TNBC- (tri-negative breast cancer) model. To investigate whether the combination of recombinant human endostatin and paclitaxel in vascular normalization time window is superior to paclitaxel alone and to analyze the role of magnetic resonance imaging (MRI) in the early evaluation of chemotherapy. Methods: human TNBC cell line MDA-MB-231 was implanted in the right lower abdomen of 36 female BALB/c-nu nude mice and was randomly divided into 4 groups (model group, recombinant human endostatin treatment group). Paclitaxel treatment group and human endostatin combined with paclitaxel treatment group, 7 rats in each group completed the experiment. Recombinant human endostatin was administered at the beginning of the experiment for 17 days and paclitaxel was administered on the 6th and 12th day respectively. All the drugs were intraperitoneally injected with the dosage of 10 mg 路kg ~ (-1) 路d ~ (-1) 路L ~ (-1) 路d ~ (-1) 路min ~ (-1) 路d ~ (-1) 路L ~ (-1) 路L ~ (-1). MRI scanning was performed 1 day before treatment and 51117 days after injection of experimental reagent. All the tumor-bearing mice were killed after the last MRI scan, the tumor was removed, the tumor was examined by pathology and immunohistochemistry, the microvessel density (MVD) and the expression of Ki67 were measured. Results: on the 17th day, the volume of transplanted tumor in combination group was smaller than that in model group and recombinant human endostatin treatment group (P 0.05), but there was no significant difference compared with paclitaxel group. On the 11th day, the slow diffusion coefficient of paclitaxel group was higher than that of model group, and that of combination group was higher than that of recombinant human endostatin treatment group (P 0.05). No distant metastases were found in the tumor bearing mice in each group. He staining showed that the tumor periphery of the four groups were obviously necrotic, and the necrosis degree of the drug treatment group was higher than that of the model group. The MVD of the drug treatment group was lower than that of the model group, and that of the combined drug group was lower than that of the drug monotherapy group (P 0.05). The expression of Ki67 in the combined drug group was significantly lower than that in the recombinant human endostatin group, but there was no significant difference compared with the paclitaxel group. Conclusion: in the time window of vascular normalization, recombinant human endostatin combined with paclitaxel chemotherapy has obvious inhibitory effect on TNBC transplanted tumor, but the curative effect is not better than paclitaxel, and slow dispersion coefficient can predict the therapeutic effect early.
【作者單位】： 暨南大學(xué)附屬第一醫(yī)院乳腺外科;暨南大學(xué)附屬第一醫(yī)院影像學(xué)科;暨南大學(xué)附屬第一醫(yī)院胃腸外科;暨南大學(xué)附屬第一醫(yī)院病理科;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81472849)
【分類(lèi)號(hào)】：R-332;R737.9

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